DESCRIPTION: This is a competitive renewal to continue Dr. Jacobson's studies into alterations in NAD metabolism following exposure to chemical carcinogens. Specifically, the objective of this application is to understand mechanisms of ADP-ribosylation following exposure to an alkylating toxin. Three aims have been proposed. The first is to systematically characterize noncovalent interactions of ADPR polymers with chromatin proteins, with the goal of elucidating factors that govern these interactions. Adiitionally, the chromatin proteins that interact noncovalently with ADPR polymers in intact cells will be identified. The second aim is to determine the structure of poly ADPR glycohydrolase, and assess its function in cellular recovery from DNA damage. The final aim will characterize carcinogen-induced protein glycation by ADPR, and to examine the role of protein ADPR lyase and/or other enzymes in the removal of ADPR polymer remnants and/or products of glycation.